A formidable challenge confronting clinical immunology is the development of synthetic vaccines that could offer advantages over traditional methods in safety, reliability and cost. Appropriate delivery of protein and peptide antigens to the immune system has proved to be a major technical hurdle. The search for tractable solutions to this problem has received significant impetus in recent years by the development of biodegradable polymers as delivery vehicles. In this grant, we introduce poly(ester amide) co-polymers as a valuable addition to the current armory of suitable delivery polymers and present supportive initial proof-of-concept experiments that demonstrate the use of these polymers as a component of a protective vaccine for influenza. Specifically, these polymer-protein vaccine formulations can be rapidly modified to match alterations in influenza strains. The recent emergence of more virulent strains and the potential for a pandemic make it important that all new vaccine candidates be developed and tested. The experiments proposed here will define the capacity of PEA polymers to deliver polypeptide viral antigens by measuring both T cell stimulation and antibody production in response to diminished protein dosage. We propose to test polymer-coupled hemagglutinin and nucleoprotein antigens derived from H1N1 influenza for optimized dosage and schedule for influenza protection in mice. (Aim 1). We will test the ability of the vaccine candidates to protect animals from other influenza strains in mouse challenge studies (Aim 2). Finally, we will prepare the optimized formulations in several forms to assess their stability to storage in order to best prepare large quantities to use for human trials.(Aim 3) Successful achievement of these aims will provide impetus for development of commercially viable influenza vaccines that are rapidly prepared, stable in storage, and facile to transport to remote locales. [unreadable] [unreadable] [unreadable]